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Q64536

- PDK2_RAT

UniProt

Q64536 - PDK2_RAT

Protein

[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial

Gene

Pdk2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 116 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    Functioni

    Serine/threonine kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis.5 Publications

    Catalytic activityi

    ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate.6 Publications

    Enzyme regulationi

    Activity increases in response to increased acetyl-CoA and NADH levels and upon binding to the pyruvate dehydrogenase subunit DLAT. Inhibited by ADP and pyruvate; these compounds interfere with DLAT binding and thereby inhibit kinase activity. Inhibited by dichloroacetate. Inhibited by AZD7545; this compound interferes with DLAT binding and thereby inhibits kinase activity. Reactive oxygen species cause the formation of disulfide bonds, and thereby inhibit the enzyme.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei290 – 2901ATP

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi251 – 2588ATP
    Nucleotide bindingi309 – 3102ATP
    Nucleotide bindingi325 – 3306ATP

    GO - Molecular functioni

    1. ATP binding Source: RGD
    2. protein complex binding Source: RGD
    3. protein heterodimerization activity Source: RGD
    4. protein homodimerization activity Source: RGD
    5. protein serine/threonine kinase activity Source: UniProtKB
    6. pyruvate dehydrogenase (acetyl-transferring) kinase activity Source: UniProtKB

    GO - Biological processi

    1. cellular response to nutrient Source: UniProtKB
    2. glucose homeostasis Source: UniProtKB
    3. glucose metabolic process Source: UniProtKB-KW
    4. insulin receptor signaling pathway Source: UniProtKB
    5. peptidyl-serine phosphorylation Source: UniProtKB
    6. protein phosphorylation Source: RGD
    7. regulation of acetyl-CoA biosynthetic process from pyruvate Source: UniProtKB
    8. regulation of cellular ketone metabolic process Source: UniProtKB
    9. regulation of gluconeogenesis Source: UniProtKB
    10. regulation of glucose metabolic process Source: UniProtKB
    11. regulation of pH Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Carbohydrate metabolism, Glucose metabolism

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (EC:2.7.11.2)
    Alternative name(s):
    PDK P45
    Pyruvate dehydrogenase kinase isoform 2
    Short name:
    PDH kinase 2
    Gene namesi
    Name:Pdk2
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi69428. Pdk2.

    Subcellular locationi

    Mitochondrion matrix 1 Publication

    GO - Cellular componenti

    1. mitochondrial pyruvate dehydrogenase complex Source: UniProtKB
    2. mitochondrion Source: RGD
    3. pyruvate dehydrogenase complex Source: RGD

    Keywords - Cellular componenti

    Mitochondrion

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini? – 407[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrialPRO_0000023442
    Transit peptidei1 – ?MitochondrionSequence Analysis

    Proteomic databases

    PaxDbiQ64536.
    PRIDEiQ64536.

    Expressioni

    Tissue specificityi

    Detected in heart (at protein level). Highest level of expression in heart and skeletal muscle and the lowest in spleen and lung. Liver, kidney, brain and testis levels are intermediate.3 Publications

    Gene expression databases

    GenevestigatoriQ64536.

    Interactioni

    Subunit structurei

    Homodimer, and heterodimer with PDK1. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3).4 Publications

    Protein-protein interaction databases

    IntActiQ64536. 1 interaction.
    STRINGi10116.ENSRNOP00000005641.

    Structurei

    Secondary structure

    1
    407
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi13 – 153
    Helixi16 – 249
    Helixi33 – 397
    Beta strandi41 – 433
    Helixi46 – 6823
    Helixi73 – 764
    Helixi79 – 9618
    Turni97 – 1004
    Helixi106 – 12217
    Turni123 – 1253
    Helixi126 – 14116
    Helixi145 – 17632
    Beta strandi185 – 1884
    Beta strandi191 – 1966
    Helixi197 – 21519
    Beta strandi222 – 23110
    Beta strandi237 – 2404
    Helixi242 – 26221
    Beta strandi267 – 2693
    Beta strandi273 – 2797
    Beta strandi281 – 29010
    Helixi297 – 3004
    Helixi301 – 3044
    Turni306 – 3094
    Helixi329 – 33911
    Beta strandi343 – 3497
    Turni350 – 3523
    Beta strandi353 – 36311
    Turni364 – 3663
    Helixi376 – 3805

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1JM6X-ray2.50A/B1-407[»]
    3CRKX-ray2.30A/B1-407[»]
    3CRLX-ray2.61A/B1-407[»]
    ProteinModelPortaliQ64536.
    SMRiQ64536. Positions 12-404.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ64536.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini135 – 364230Histidine kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the PDK/BCKDK protein kinase family.Curated
    Contains 1 histidine kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG0642.
    HOGENOMiHOG000164315.
    HOVERGENiHBG000511.
    InParanoidiQ64536.
    KOiK00898.
    PhylomeDBiQ64536.

    Family and domain databases

    Gene3Di1.20.140.20. 1 hit.
    3.30.565.10. 1 hit.
    InterProiIPR018955. BCDHK/PDK_N.
    IPR003594. HATPase_ATP-bd.
    IPR005467. Sig_transdc_His_kinase_core.
    [Graphical view]
    PfamiPF10436. BCDHK_Adom3. 1 hit.
    PF02518. HATPase_c. 1 hit.
    [Graphical view]
    SMARTiSM00387. HATPase_c. 1 hit.
    [Graphical view]
    SUPFAMiSSF55874. SSF55874. 1 hit.
    SSF69012. SSF69012. 1 hit.
    PROSITEiPS50109. HIS_KIN. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q64536-1 [UniParc]FASTAAdd to Basket

    « Hide

    MRWFRALLKN ASLAGAPKYI EHFSKFSPSP LSMKQFLDFG SSNACEKTSF    50
    TFLRQELPVR LANIMKEINL LPDRVLSTPS VQLVQSWYVQ SLLDIMEFLD 100
    KDPEDHRTLS QFTDALVTIR NRHNDVVPTM AQGVLEYKDT YGDDPVSNQN 150
    IQYFLDRFYL SRISIRMLIN QHTLIFDGST NPAHPKHIGS IDPNCSVSDV 200
    VKDAYDMAKL LCDKYYMASP DLEIQEVNAT NATQPIHMVY VPSHLYHMLF 250
    ELFKNAMRAT VESHESSLTL PPIKIMVALG EEDLSIKMSD RGGGVPLRKI 300
    ERLFSYMYST APTPQPGTGG TPLAGFGYGL PISRLYAKYF QGDLQLFSME 350
    GFGTDAVIYL KALSTDSVER LPVYNKSAWR HYQTIQEAGD WCVPSTEPKN 400
    TSTYRVS 407
    Length:407
    Mass (Da):46,106
    Last modified:November 1, 1996 - v1
    Checksum:iA01C377290A69EF4
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U10357 mRNA. Translation: AAB54084.1.
    BC061823 mRNA. Translation: AAH61823.1.
    PIRiA55305.
    RefSeqiNP_110499.1. NM_030872.1.
    UniGeneiRn.88597.

    Genome annotation databases

    GeneIDi81530.
    KEGGirno:81530.
    UCSCiRGD:69428. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U10357 mRNA. Translation: AAB54084.1 .
    BC061823 mRNA. Translation: AAH61823.1 .
    PIRi A55305.
    RefSeqi NP_110499.1. NM_030872.1.
    UniGenei Rn.88597.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1JM6 X-ray 2.50 A/B 1-407 [» ]
    3CRK X-ray 2.30 A/B 1-407 [» ]
    3CRL X-ray 2.61 A/B 1-407 [» ]
    ProteinModelPortali Q64536.
    SMRi Q64536. Positions 12-404.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q64536. 1 interaction.
    STRINGi 10116.ENSRNOP00000005641.

    Chemistry

    BindingDBi Q64536.
    ChEMBLi CHEMBL2096663.

    Proteomic databases

    PaxDbi Q64536.
    PRIDEi Q64536.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 81530.
    KEGGi rno:81530.
    UCSCi RGD:69428. rat.

    Organism-specific databases

    CTDi 5164.
    RGDi 69428. Pdk2.

    Phylogenomic databases

    eggNOGi COG0642.
    HOGENOMi HOG000164315.
    HOVERGENi HBG000511.
    InParanoidi Q64536.
    KOi K00898.
    PhylomeDBi Q64536.

    Miscellaneous databases

    EvolutionaryTracei Q64536.
    NextBioi 615077.

    Gene expression databases

    Genevestigatori Q64536.

    Family and domain databases

    Gene3Di 1.20.140.20. 1 hit.
    3.30.565.10. 1 hit.
    InterProi IPR018955. BCDHK/PDK_N.
    IPR003594. HATPase_ATP-bd.
    IPR005467. Sig_transdc_His_kinase_core.
    [Graphical view ]
    Pfami PF10436. BCDHK_Adom3. 1 hit.
    PF02518. HATPase_c. 1 hit.
    [Graphical view ]
    SMARTi SM00387. HATPase_c. 1 hit.
    [Graphical view ]
    SUPFAMi SSF55874. SSF55874. 1 hit.
    SSF69012. SSF69012. 1 hit.
    PROSITEi PS50109. HIS_KIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning of the p45 subunit of pyruvate dehydrogenase kinase."
      Popov K.M., Kedishvili N.Y., Zhao Y., Gudi R., Harris R.A.
      J. Biol. Chem. 269:29720-29724(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, TISSUE SPECIFICITY.
      Tissue: Heart.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Prostate.
    3. "Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex."
      Bowker-Kinley M.M., Davis W.I., Wu P., Harris R.A., Popov K.M.
      Biochem. J. 329:191-196(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, TISSUE SPECIFICITY.
    4. "Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase."
      Korotchkina L.G., Patel M.S.
      J. Biol. Chem. 276:37223-37229(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, FUNCTION.
    5. "Interaction between the individual isoenzymes of pyruvate dehydrogenase kinase and the inner lipoyl-bearing domain of transacetylase component of pyruvate dehydrogenase complex."
      Tuganova A., Boulatnikov I., Popov K.M.
      Biochem. J. 366:129-136(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DLAT.
    6. "AZD7545, a novel inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2), activates pyruvate dehydrogenase in vivo and improves blood glucose control in obese (fa/fa) Zucker rats."
      Mayers R.M., Butlin R.J., Kilgour E., Leighton B., Martin D., Myatt J., Orme J.P., Holloway B.R.
      Biochem. Soc. Trans. 31:1165-1167(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. "Formation of functional heterodimers by isozymes 1 and 2 of pyruvate dehydrogenase kinase."
      Boulatnikov I., Popov K.M.
      Biochim. Biophys. Acta 1645:183-192(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, FUNCTION, INTERACTION WITH PDK1, SUBUNIT.
    8. "Inactivation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species."
      Hurd T.R., Collins Y., Abakumova I., Chouchani E.T., Baranowski B., Fearnley I.M., Prime T.A., Murphy M.P., James A.M.
      J. Biol. Chem. 287:35153-35160(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ENZYME REGULATION, TISSUE SPECIFICITY.
    9. "Structure of pyruvate dehydrogenase kinase. Novel folding pattern for a serine protein kinase."
      Steussy C.N., Popov K.M., Bowker-Kinley M.M., Sloan R.B. Jr., Harris R.A., Hamilton J.A.
      J. Biol. Chem. 276:37443-37450(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH ADP.
    10. "Structural and functional insights into the molecular mechanisms responsible for the regulation of pyruvate dehydrogenase kinase 2."
      Green T., Grigorian A., Klyuyeva A., Tuganova A., Luo M., Popov K.M.
      J. Biol. Chem. 283:15789-15798(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH ATP ANALOG AND DLAT, CATALYTIC ACTIVITY, SUBUNIT.

    Entry informationi

    Entry nameiPDK2_RAT
    AccessioniPrimary (citable) accession number: Q64536
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 116 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3